EFFECTS OF A SPIDER TOXIN AND ITS ANALOG ON GLUTAMATE-ACTIVATED CURRENTS IN THE HIPPOCAMPAL CA1 NEURON AFTER ISCHEMIA

1. We studied the effects of polyamine toxins derived from a spider ve nom on CAI pyramidal neurons in gerbil hippocampal slices by patch-cla mp recording. Joro spider toxin (JSTX) and its synthetic analogue, 1-n aphthyl acetyl spermine (Naspm), which are known to block non-N-methyl -D-aspartate (non-NMDA) receptor in a subunit specific manner, were us ed. 2,Naspm depressed the excitatory postsynaptic currents (EPSCs) med iated by non-NMDA receptor channels. A further reduction of EPSCs occu rred with addition of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Con versely, when CNQX was applied first, no further depression of EPSCs o ccurred on addition of Naspm, indicating that Naspm blocks a fraction of the CNQX-sensitive non-NMDA-receptor-mediated currents. 3. After is chemia, the time course of EPSCs of CA1 pyramidal neurons was slowed a nd Naspm depressed the slow EPSCs more strongly than those in control neurons. 4. Analysis of single-channel currents by outside-out patch-c lamp recording from ischemic CA1 neurons revealed that Naspm blocked a subpopulation of ha-amino-3-hydroxy-5-methylisoxazole-4-propionate- a nd kainate-induced single-channel currents. 5. Because the EPSCs in CA L neurons after ischemia are mediated by Ca2+-permeable non-MCIDA rece ptor-mediated conductances, the present results indicate that Naspm an d JSTX are effective at blocking abnormal EPSCs that may induce Ca2+ a ccumulation leading to delayed neuronal death after transient ischemic insult.